Motor Nerve Conduction Block Estimation in Demyelinating Neuropathies by Deconvolution

A deconvolution method is proposed for conduction block (CB) estimation based on two compound muscle action potentials (CMAPs) elicited by stimulating a nerve proximal and distal to the region in which the block is suspected. It estimates the time delay distributions by CMAPs deconvolution, from which CB is computed. The slow afterwave (SAW) is included to describe the motor unit potential, as it gives an important contribution in case of the large temporal dispersion (TD) often found in patients. The method is tested on experimental signals obtained from both healthy subjects and pathological patients, with either Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or Multifocal Motor Neuropathy (MMN). The new technique outperforms the clinical methods (based on amplitude and area of CMAPs) and a previous state-of-the-art deconvolution approach. It compensates phase cancellations, allowing to discriminate among CB and TD: estimated by the methods of amplitude, area and deconvolution, CB showed a correlation with TD equal to 39.3%, 29.5% and 8.2%, respectively. Moreover, a significant decrease of percentage reconstruction errors of the CMAPs with respect to the previous deconvolution approach is obtained (from a mean/median of 19.1%/16.7% to 11.7%/11.2%). Therefore, the new method is able to discriminate between CB and TD (overcoming the important limitation of clinical approaches) and can approximate patients’ CMAPs better than the previous deconvolution algorithm. Then, it appears to be promising for the diagnosis of demyelinating polyneuropathies, to be further tested in the future in a prospective clinical trial.

Circulating testosterone and dehydroepiandrosterone are associated with individual motor unit features in untrained and highly active older men

Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) characteristics in older men, including masters athletes competing in endurance and power events. Forty-three older men (mean ± SD age: 69.9 ± 4.6 years) were studied based on competitive status. The serum concentrations of dehydroepiandrosterone (DHEA), total testosterone (T) and estradiol were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from vastus lateralis (VL) during 25% of maximum voluntary isometric contractions and processed to extract MU firing rate (FR), and motor unit potential (MUP) features. After adjusting for athletic status, MU FR was positively associated with DHEA levels (p = 0.019). Higher testosterone and estradiol were associated with lower MUP complexity; these relationships remained significant after adjusting for athletic status (p = 0.006 and p = 0.019, respectively). Circulating DHEA was positively associated with MU firing rate in these older men. Higher testosterone levels were associated with reduced MUP complexity, indicating reduced electrophysiological temporal dispersion, which is related to decreased differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting human motor units in older age.

Inclusion body myositis: correlation of clinical outcomes with histopathology, electromyography and laboratory findings

Objective To determine whether histopathological, electromyographic and laboratory markers correlate with clinical measures in Inclusion Body Myositis (IBM) Methods We reviewed our electronic medical records to identify patients with IBM according to ENMC 2011 criteria, seen between 2015 and 2020. We only included patients who had a muscle biopsy and needle electromyography (EMG) performed on the same muscle (opposite or same side). We used a detailed grading system (0- normal to 4- severe) to score histopathological and EMG findings. Clinical severity was assessed by the modified Rankin scale (mRS), muscle strength sum score (SSS), quadriceps strength and severity of dysphagia on swallow evaluation. Serum markers of interest were creatine kinase level, and cN-1A antibodies. Results We included 50 IBM patients, with a median age of 69 years; 64% were males. Median disease duration at diagnosis was 51 months. On muscle biopsy, endomysial inflammation mainly correlated with dysphagia, and inversely correlated with mRS. Vacuoles and congophilic inclusions did not correlate with any of the clinical measures. On EMG, the shortness of motor unit potential (MUP) duration correlated with all clinical measures. Myotonic discharges, and not fibrillation potentials, correlated with the severity of inflammation. Serum markers did not have a statistically-significant correlation with any of the clinical measures. Conclusions Dysphagia was the main clinical feature of IBM correlating with endomysial inflammation. Otherwise, inclusion body myositis clinical measures had limited correlation with histopathological features in this study. The shortness of MUP duration correlated with all clinical measures.

Quantitative motor unit potential analysis and nerve conduction studies for detection of subclinical peripheral nerve dysfunction in patients with compensated liver cirrhosis

Background Peripheral neuropathy is an underestimated problem of compensated liver cirrhosis despite its negative effect on quality of life. The aim was to assess the role of meticulous electrophysiological screening (nerve conduction responses and quantitative motor unit potential analysis) of subclinical peripheral nerve dysfunction in patients with compensated cirrhosis and also to explore its relations with different characteristics of liver disease. Severity of cirrhosis was assessed by Child–Pugh and albumin-bilirubin (ALBI) scores. Results Prevalence of hepatic neuropathy (HN) was 82%. It involved sensory and motor fibers (66%), and its pathophysiology was axonal (53.7%) or mixed axonal and demyelinating (46.3). The most sensitive discriminating tests were ulnar sensory conduction velocity (area under curve (AUC) = 0.915) and peak latency (AUC = 0.887), peroneal motor conduction velocity (AUC = 0.885), ulnar distal motor latency (AUC = 0.842), and first dorsal interosseous number of phases (AUC = 0.736). HN showed significant correlation with the severity of liver disease assessed by both child (P = 0.029) and ALBI (P = 0.016) scores and also correlated with the low serum albumin level (P = 0.001). Conclusions Subclinical mild axonal polyneuropathy is very common in post-hepatitis C compensated cirrhosis picked up by meticulous electrophysiological testing, and it is related to severity of liver cirrhosis and low serum albumin level.

LSTM Neural Network for Inferring Conduction Velocity Distribution in Demyelinating Neuropathies

Waveform analysis of compound muscle action potential (CMAP) is important in the detailed analysis of conduction velocities of each axon as seen in temporal dispersion. This understanding is limited because conduction velocity distribution cannot be easily available from a CMAP waveform. Given the recent advent of artificial intelligence, this study aimed to assess whether conduction velocity (CV) distribution can be inferred from CMAP by the use of deep learning algorithms. Simulated CMAP waveforms were constructed from a single motor unit potential and randomly created CV histograms (n = 12,000). After training the data with various recurrent neural networks (RNNs), CV inference was tested by the network. Among simple RNNs, long short-term memory (LSTM) and gated recurrent unit, the best accuracy and loss profiles, were shown by two-layer bidirectional LSTM, with training and validation accuracies of 0.954 and 0.975, respectively. Training with the use of a recurrent neural network can accurately infer conduction velocity distribution in a wide variety of simulated demyelinating neuropathies. Using deep learning techniques, CV distribution can be assessed in a non-invasive manner.

Safety, Tolerability, and Effect of Nusinersen Treatment in Ambulatory Adults With 5q-SMA

Objective: To determine the safety and tolerability of nusinersen treatment in ambulatory adults with spinal muscular atrophy (SMA) and investigate the treatment effect on muscle strength, physical function, and motor unit physiology.Methods: Individuals aged 18 years or older with genetically confirmed 5q SMA, three or more copies of the SMN2 gene, and the ability to ambulate 30 feet were enrolled. Safety outcomes included the number of adverse events and serious adverse events, clinically significant vital sign or laboratory parameter abnormalities. Outcome assessments occurred at baseline (prior to the first dose of nusinersen) and then 2, 6, 10, and 14 months post-treatment.Results: Six women, seven men (mean age: 37 ± 11, range: 18–59 years) were included for analyses. The most common side effects were headache and back pain, but overall procedures and treatments were well-tolerated. No serious adverse events were reported. Maximal Voluntary Isometric Muscle Contraction Testing (MVICT) and 6-min walk test (6MWT) both showed overall stability with significant increases at 2, 6, and 10 months for the 6MWT. More consistent significant treatment effects were noted on the Hammersmith Functional Motor Scale Expanded, SMA-Functional Rating Scale, and forced vital capacity. Treatment resulted in progressively increased ulnar compound muscle action potential and average single motor unit potential amplitudes, but motor unit number estimation remained stable.Conclusions: Nusinersen treatment is safe and well-tolerated in ambulatory adults with SMA. Treatment resulted in improved motor function and electrophysiological findings suggest that this improvement may be occurring via improved motor unit reinnervation capacity.

Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy

Objective: Investigation of the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with spinal muscular atrophy (SMA).Methods: Non-ambulatory individuals, aged 18 years or older with genetically confirmed 5q SMA were enrolled. In participants with spinal fusion, fluoroscopy guided cervical C1–C2 lateral approach was used. Outcomes at 2, 6, 10, and 14 months post-treatment were compared with baseline assessment. Forced vital capacity (FVC) was the primary outcome, and RULM, HFMSE, the modified SMA-FRS, and ulnar nerve electrophysiology [compound muscle action potential (CMAP), single motor unit size, and motor unit number] were secondary. Adverse and serious adverse events and clinically significant vital sign or lab abnormalities were recorded.Results: Results from 12 women and 7 men (mean age: 39.7 ± 13.9, range: 21–64 years) were analyzed. No clinically significant changes of vital signs or laboratory parameters were observed. Five participants were hospitalized for pneumonia. Other adverse events included headache, back pain, cervical injection site pain, and upper respiratory and urinary tract infections. High baseline protein/creatinine ratio without significant change on treatment noted in 4 participants. FVC was feasible in all participants. HFMSE and RULM were not feasible in the majority of participants. FVC and functional outcomes were stable without improvement. CMAP and single motor unit potential sizes showed enlargement while motor unit numbers were stable.Conclusions: Nusinersen, including C1/C2 delivery, was safe overall and well-tolerated. Several outcome measures were limited by floor effect. Overall, treatment resulted in stability of motor outcomes, but motor unit and CMAP size were increased.

Lifelong exercise is associated with more homogeneous motor unit potential features across deep and superficial areas of vastus lateralis

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Isolated Musculocutaneous Nerve Injury in a Professional Baseball Player: A Case Report

Introduction: Musculocutaneous nerve lesion in a throwing athlete is a rare condition. We report the case of a professional baseball pitcher with an isolated musculocutaneous nerve lesion that occurred during a pitching motion. Case Presentation: The patient had radiating pain in the upper arm and weakness of elbow flexion. Physical examination revealed flaccid paralysis of the biceps brachii muscle and paresthesia in the right lateral forearm. Musculocutaneous nerve injury was suspected. Because some signs of recovery were observed within a few days, the patient received non-operative management. Nerve conduction studies at 2 weeks after the injury showed low-amplitude compound muscle action potential of the right biceps brachii muscle by stimulation of the musculocutaneous nerve. Needle electromyography showed markedly reduced motor unit potential recruitment in the biceps brachii muscle. He was diagnosed as having isolated musculocutaneous nerve injury. At 2 months after the injury, the muscle contraction and strength of the biceps brachii muscle improved. At 7 months after the injury, muscle weakness was fully recovered. His pitching ability returned to that of a competitive player. Conclusion: Because the neuroparalysis was incomplete and began to recover within a few days, we considered the pathology of this injury to be incomplete axonotmesis, which was successfully treated conservatively. Keywords: Isolated musculocutaneous nerve injury, baseball pitcher, axonotmesis.